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Discovery could show why cancer vaccines have failed

Nov 8, 2010 3:40pm

Cambridge researchers believe they have stumbled upon why scientists have struggled in using the immune system to fight tumors. New research has shown that a type of stromal cell found in many cancers that expresses fibroblast activation protein alpha (FAP), plays a major role in suppressing the immune response in cancerous tumors. However, if these cells are destroyed, the immune system can control the previously uncontrolled tumor.

"Finding the specific cells within the complex mixture of the cancer stroma that prevents immune killing is an important step," says Douglas Fearon, Sheila Joan Smith Professor of Immunology of the Department of Medicine at the University of Cambridge, in a statement. "Further studying how these cells exert their effects may contribute to improved immunological therapies by allowing us to remove a barrier that the cancer has constructed."

In order to determine whether FAP-expressing stromal cells contribute to the resistance of a tumor to vaccination, the researchers created a transgenic mouse model that allowed them to destroy cells expressing FAP. When FAP-expressing cells were destroyed in tumors in mice with a certain type of lung carcinomas--of which only two percent of the tumor cells are FAP-expressing--the cancer began to rapidly 'die.' The researchers hope to collaborate with scientists at the CRUK Cambridge Research Institute to evaluate the effects of depleting FAP-expressing cells in a mouse model that more closely resemble human cancer.